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Amyloid beta-Protein Aggregation Produces Highly Reproducible Kinetic Data and Occurs by a Two-Phase Process

Hellstrand, Erik LU ; Boland, Barry; Walsh, Dominic M. and Linse, Sara LU (2010) In ACS Chemical Neuroscience 1(1). p.13-18
Abstract
Protein aggregation can lead to major disturbances of cellular processes and is associated with several diseases. We report kinetic and equilibrium data by ThT fluorescence and enzyme-linked immunosorbent assay of sufficient quality and reproducibility to form a basis for mechanistic understanding of amyloid beta-peptide (A beta) fibril formation. Starting from monomeric peptide in a pure buffer system without cosolvents, we find that the kinetics of A beta aggregation vary strongly with peptide concentration in a highly predictable manner. The free A beta concentration in equilibrium with fibrils was found to vary with total peptide concentration in a manner expected for a two-phase system. The free versus total A beta concentration was... (More)
Protein aggregation can lead to major disturbances of cellular processes and is associated with several diseases. We report kinetic and equilibrium data by ThT fluorescence and enzyme-linked immunosorbent assay of sufficient quality and reproducibility to form a basis for mechanistic understanding of amyloid beta-peptide (A beta) fibril formation. Starting from monomeric peptide in a pure buffer system without cosolvents, we find that the kinetics of A beta aggregation vary strongly with peptide concentration in a highly predictable manner. The free A beta concentration in equilibrium with fibrils was found to vary with total peptide concentration in a manner expected for a two-phase system. The free versus total A beta concentration was linear up to ca. 0.2,mu M, after which free A beta decreased with total A beta toward an asymptotic value. Our results imply that A beta fibril formation arises from a sequence of events in a highly predictable manner. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer, mechanism, kinetics, Amyloid, aggregation, fibril
in
ACS Chemical Neuroscience
volume
1
issue
1
pages
13 - 18
publisher
The American Chemical Society
external identifiers
  • wos:000277743100003
  • scopus:77951676986
ISSN
1948-7193
DOI
10.1021/cn900015v
language
English
LU publication?
yes
id
44ac5a93-b3e4-46ac-b657-1da13135d03f (old id 1617649)
date added to LUP
2010-06-21 11:45:30
date last changed
2018-07-15 03:48:48
@article{44ac5a93-b3e4-46ac-b657-1da13135d03f,
  abstract     = {Protein aggregation can lead to major disturbances of cellular processes and is associated with several diseases. We report kinetic and equilibrium data by ThT fluorescence and enzyme-linked immunosorbent assay of sufficient quality and reproducibility to form a basis for mechanistic understanding of amyloid beta-peptide (A beta) fibril formation. Starting from monomeric peptide in a pure buffer system without cosolvents, we find that the kinetics of A beta aggregation vary strongly with peptide concentration in a highly predictable manner. The free A beta concentration in equilibrium with fibrils was found to vary with total peptide concentration in a manner expected for a two-phase system. The free versus total A beta concentration was linear up to ca. 0.2,mu M, after which free A beta decreased with total A beta toward an asymptotic value. Our results imply that A beta fibril formation arises from a sequence of events in a highly predictable manner.},
  author       = {Hellstrand, Erik and Boland, Barry and Walsh, Dominic M. and Linse, Sara},
  issn         = {1948-7193},
  keyword      = {Alzheimer,mechanism,kinetics,Amyloid,aggregation,fibril},
  language     = {eng},
  number       = {1},
  pages        = {13--18},
  publisher    = {The American Chemical Society},
  series       = {ACS Chemical Neuroscience},
  title        = {Amyloid beta-Protein Aggregation Produces Highly Reproducible Kinetic Data and Occurs by a Two-Phase Process},
  url          = {http://dx.doi.org/10.1021/cn900015v},
  volume       = {1},
  year         = {2010},
}